Tissue engineering and wound healing are approaches to reconstruction and/or regeneration of lost or damaged tissue. Earlier efforts at developing extracellular matrices for cell growth have included the use of biodegradable and bioabsorbable materials. In the development of these matrices, hyaluronic acid and collagen have been employed for use as engineering tissues in the replacement of organs, skin replacements for burns or ulcers, replacement of bone loss or even replacement of brain tissue. These materials are typically expensive and have variable properties when produced in large quantities.
Polymers such as polylactic acid homopolymers and polycaprolactone homopolymers, and their related copolymers and blends provide a porous structure for cell penetration and polymer degradation as scaffolds and/or extracellular matrices. However, for successful tissue regeneration, sufficient cell propagation and appropriate differentiation must be achieved in a three-dimensional cellular composite. Nonwoven fabrics have been used as scaffolds in tissue applications as described in Aigner, J. et al., “Cartilage Tissue Engineering with Novel Nonwoven Structured Biomaterial Based on Hyaluronic Acid Benzyl Ester”, J. Biomed. Mater. Res., 1998, 42, 172-181; Bhat, G. S., “Nonwovens as Three-Dimensional Textiles for Composites”, Mater. Manuf. Process, 1995, 10, 67-688; Ma, T., “Tissue Engineering Human Placenta Trophoblast Cells in 3-D Fibrous Matrix: Spatial Effects on Cell Proliferation and Function”, Biotechnol. Prog., 1999, 15, 715-724, and Bhattarai, S. R. et al., “Novel Biodegradable Electrospun Membrane: Scaffold for Tissue Engineering”, Biomaterials, 2004, 25, 2595-2602.
Cell biology entails the structure and function of cells, the basic units that make up living organisms. The form and function of the human body are the sum of the form, function, and behavior of its component cells. As a result, research in this area has grown to better understand the prevention and treatment of disease and human behavior. Technology and methodology improvements have evolved cell biology to new levels of understanding cells.
In a growing cellular system, a cycle occurs from the formation of a cell by the division of the mother cell into two daughter cells. This cycle occurs in multicellular organisms as well as in cultures of isolated cells. All of the components of the cell double during the cycle ending with the splitting events of mitosis (nuclear division) and cytokinesis (cytoplasmic division).
Cells in a multicellular organism become specialized to perform specific functions via cell differentiation. The life cycle of a higher organism begins with a unicellular stage, and becomes more complex as the individual grows and takes on its characteristic form. Differentiated cells maintain their characteristic form and identity because populations of specialized cell types remain assembled in a certain pattern. Several cell types make up a tissue, and different tissues build an organ.
The movement of cells and their cellular components are relative to its environment. The extremely diverse movements as a form of locomotion are analogous to those of amoebas. This intracellular movement is accomplished by the formation of pseudopodia, in which cytoplasm streams actively during pseudopod extension and withdrawal. In some cases, the cells are known to exert forces that change the shape of developing tissues and organs of embryos. The cells crawl through body cavities, lymph channels, and tissue spaces to seek out and engulf bacteria, foreign matter, and dead or dying cells. In wound healing activities, the adjacent cells crawl across the wound surface, covering it while other cells infiltrate and fill in the gaps. Tissue cells crawl very slowly at a speed of about 0.5 to 50 micrometers/minute, whereas, structural cells such as fibroblasts advance their own length in an hour or so, moving approximately 1 to 2 mm/day. More information about cells and cell biology can be found in McGraw-Hill Encyclopedia of Science & Technology, 1987, 3, 317-384.
In developing a matrix for cell growth, cell differentiation and proliferation is often difficult with respect to conventional culture techniques. The cultured cells normally are isolated from their tissue specific extracellular matrix followed by suspension in a growth medium where they adhere to the bottom of a culture dish to form a confluent monolayer. Cells often lose their morphology as well as their biochemical and functional properties. As a result, dedifferentiated cells may behave differently compared to their original tissue environment. In order for cellular proliferation and differentiation on to occur, attachment must occur to the scaffold with sufficient surface area. The scaffold or matrix surface may be modified with a peptide sequence to promote recognition and rapid adhesion of the cells. Furthermore, the three dimensional matrix requires a porous structure which can allow nutrients and gases to diffuse into a mass of cells attached to the flakes. The free exchange of nutrients, gases and waste to and from the cells proliferating throughout the scaffold is necessary to maintain cell viability. This allows the matrix to act as a carrier for the differentiation and proliferation for extended periods of time.